Comparison of five selective media for identifying fecal carriage of vancomycin-resistant enterococci.

There is no uniformly accepted method for detecting colonization with vancomycin-resistant enterococci (VRE). The sensitivities of five culture methods were determined for patients known to harbor VRE. Of 189 inpatients, 101 were found to harbor VRE by at least one method. Three methods detected fewer than half of the cultures. Campylobacter agar identified 70% of patients. Enterococcosel broth (containing vancomycin and aztreonam) identified 88% and may be preferred over other media for routine surveillance.     

Simple and complex antibody reactions in radioimmunoassay and the prediction of assay characteristics

Radioimmunoassays are usually developed empirically since there have been few established rules which cover general RIA behaviour. Evidence is presented which enables the delineation of 2 types of RIA with distinct group characteristics. (1) Simple RIA, conforming to the law of mass-action kinetics, is a result of univalent interaction. Examples of simple RIA include hapten assays and those using a monoclonal antibody (McAb). (2) Complex RIA occurs when antigen reacts multivalently with a polyclonal antiserum (PcAs). The formation of multicomponent complexes between a large molecular weight antigen and a PcAs is demonstrated using gel exclusion chromatography. These complexes are resistant to dissociation and are responsible for higher affinity, greater sensitivity and slower equilibration times compared to simple RIA. The assignment of an assay to either the simple or complex RIA group is dependent upon either the molecular size of the antigen or the use of a McAb. The consequent predictability of RIA behaviour enables a more rational approach to optimal assay design than current theory allows. It is advocated that the inability of a McAb to form multicomponent complexes is a major disincentive to their indiscriminate adoption in RIA.     

Emphysema in the renal allograft

Two diabetic patients in whom emphysematous pyelonephritis developed after renal transplantation are described. Clinical recognition of this unusual and serious infection is masked by the effects of immunosuppression. Abdominal radiographic, ultrasound, and computed tomography findings are discussed. The clinical presentation includes urinary tract infection, sepsis, and acute tubular malfunction of the allograft in insulin-dependent diabetics.     

Central muscle relaxant properties of 2,6-dimethylphenethylurea and related compounds

Twenty-eight phenylalkylureas with alkyl, hydroxy, methoxy or chloro-substituents in the aryl ring have been synthesized and tested for central depressant and muscle relaxant properties. In this series, the dimethylphenethylureas with at least one ortho-methyl group show unexpectedly selective muscle relaxant activity. 2,6-Dimethylphenethylurea inhibits polysynaptic reflexes more readily than monosynaptic ones, but also depresses muscle contractions by an action independent of its effect on interneuronal transmission. It is a weak anticonvulsant, suppresses rage episodes in “fighting” mice, and has no selective blocking action on conditioned responses. It thus has a pharmacological profile resembling those of mephenesin and meprobamate, but distinct from either, and differing still more from those of phenobarbitone, chlordiazepoxide or chlorpromazine. However, tolerance to its action develops readily.     

Further studies of rimiterol and salbutamol administered by intermittent positive-pressure ventilation, and an important observation on the technique of using the Bennett ventilator.

1. Using the same technique of administering drugs by intermittent positive-pressure ventilation as used in previous studies a source of contamination of solutions nebulized was discovered. This was rectified by using a new ventilator and completely separate patient circuits for each solution nebulized. 2 Salbutamol 0.5% and 0.25% solutions achieved the same degree of bronchodilatation, but there was a significantly greater increase in heart rate produced by salbutamol 0.5%. 3 Rimiterol 0.5% and salbutamol 0.25% produced similar peak mean improvements in FEV and also induced the same degree of tachycardia, but the duration of these effects were significantly shorter in the case of rimiterol. 4 The sustained degree of bronchodilatation achieved by salbutamol 0.25% could not be mirrored by giving two doses of rimiterol 0.5%, the second dose 2 h after the first. 5 Rimiterol 0.5% induced a degree of tachycardia which was similar in peak effect to that observed after salbutamol 0.25%. However, in the controls the second dose of rimiterol, given 2 h after the first, was responsible for only a small increase in heart rate which was not significantly different than that after saline in the other three treatment groups.     

A population-based study of anxiety as a precursor for depression in childhood and adolescence

Background  

Anxiety and depression co-occur in children and adolescents with anxiety commonly preceding depression. Although there is some evidence to suggest that the association between early anxiety and later depression is explained by a shared genetic aetiology, the contribution of environmental factors is less well examined and it is unknown whether anxiety itself is a phenotypic risk factor for later depression. These explanations of the association between early anxiety and later depression were evaluated.     

Nonadherence as a predictor of antidiabetic drug therapy intensification (augmentation)

PURPOSE: To determine if nonadherence with antidiabetic drug therapy is predictive of subsequent antidiabetic drug therapy intensification. METHODS: We conducted a retrospective cohort study examining retail pharmacy dispensings of sulfonylureas or metformin to 1067 patients having diabetes. Patients that did not receive a sufficient quantity of medication to cover at least 80% of days during the evaluation period were classified as nonadherent. Outcomes identified were increase in the dose of antidiabetic medication utilized, the addition of a second antidiabetic agent to the regimen or either. RESULTS: Among users of sulfonylurea monotherapy, those classified as nonadherent were 45% more likely to intensify therapy in subsequent months as compared with those classified as adherent (age-adjusted odds ratio (OR) 1.45; 95% confidence interval (CI) 1.06-2.00). This finding was largely driven by observed increases in dosage, which were more likely among patients classified as nonadherent (age-adjusted OR 1.48, 95%CI 1.07-2.05). Nonadherence was not found to be predictive of the subsequent addition of a second antidiabetic agent (OR 1.02; 95%CI 0.64-1.63). Overall findings were similar for the smaller sample of patients receiving metformin monotherapy, though observed differences did not achieve statistical significance. CONCLUSIONS: Patients who were poorly adherent to oral antidiabetic drug therapy more frequently experienced an increase in the dose of medication prescribed, as compared to patients that were classified as adherent. This finding underscores the need for prescribers to consider nonadherence as a root cause when patients fail to achieve therapeutic goals.     

Focal complex formation in adult cardiomyocytes is accompanied by the activation of beta3 integrin and c-Src

In pressure-overloaded myocardium, our recent study demonstrated cytoskeletal assembly of c-Src and other signaling proteins which was partially mimicked in vitro using adult feline cardiomyocytes embedded in three-dimensional (3D) collagen matrix and stimulated with an integrin-binding Arg-Gly-Asp (RGD) peptide. In the present study, we improved this model further to activate c-Src and obtain a full assembly of the focal adhesion complex (FAC), and characterized c-Src localization and integrin subtype(s) involved. RGD dose response experiments revealed that c-Src activation occurs subsequent to its cytoskeletal recruitment and is accompanied by p130Cas cytoskeletal binding and focal adhesion kinase (FAK) Tyr925 phosphorylation. When cardiomyocytes expressing hexahistidine-tagged c-Src via adenoviral gene delivery were used for RGD stimulation, the expressed c-Src exhibited relocation: (i) biochemical analysis revealed c-Src movement from the detergent-soluble to the -insoluble cytoskeletal fraction and (ii) confocal microscopic analysis showed c-Src movement from a nuclear/perinuclear to a sarcolemmal region. RGD treatment also caused sarcolemmal co-localization of FAK and vinculin. Characterization of integrin subtypes revealed that beta3, but not beta1, integrin plays a predominant role: (i) expression of cytoplasmic domain of beta1A integrin did not affect the RGD-stimulated FAC formation and (ii) both pressure-overloaded myocardium and RGD-stimulated cardiomyocytes exhibited phosphorylation of beta3 integrin at Tyr773/785 sites but not beta1 integrin at Thr788/789 sites. Together these data indicate that RGD treatment in cardiomyocytes causes beta3 integrin activation and c-Src sarcolemmal localization, that subsequent c-Src activation is accompanied by p130Cas binding and FAK Tyr925 phosphorylation, and that these events might be crucial for growth and remodeling of hypertrophying adult cardiomyocytes.